A systematic review of MERS-CoV (Middle East Respiratory Syndrome Coronavirus) seroprevalence and viral RNA prevalence in dromedary camels: implications for animal vaccination

Human infection with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is driven by recurring dromedary-to-human spill-over events, leading decision-makers to consider dromedary vaccination. Dromedary vaccine candidates in the development pipeline are showing hopeful results, but gaps in our understanding of the epidemiology of MERS-CoV in dromedaries must be addressed to design and evaluate potential vaccination strategies. We systematically reviewed the published literature reporting seroprevalence and/or prevalence of active MERS-CoV infection in dromedary populations from both cross-sectional and longitudinal studies, including 60 studies in our qualitative syntheses. MERS-CoV seroprevalence increased with age up to 80-100% in adult dromedaries supporting geographically wide spread endemicity of MERS-CoV in dromedaries in both the Arabian Peninsula and countries exporting dromedaries from Africa. The high prevalence of active infection measured in juveniles and at sites where dromedary populations mix should guide further investigation – particularly of dromedary movement – and inform vaccination strategy design.


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Since the first human case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection 53 was detected in 2012 (1), a substantial evidence base has built up showing dromedary camels to be the 54 zoonotic source of this virus (2). MERS-CoV circulates extensively in dromedary populations causing 55 no impactful disease. Human infection, however, is associated with a measured case fatality ratio of 56 around 35% (3). Following spillover events, human-to-human transmission of MERS-CoV is 57 relatively inefficient and limited to close, unprotected contact environments such as hospitals (4,5).

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Phylogenetic analysis of viral sequences isolated from dromedaries and humans indicates that 59 hundreds of camel-to-human spillover events are likely to have occurred since 2012 (6). Taken 60 together, recurring dromedary-to-human transmission is driving ongoing human infection.

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The key role of dromedaries in human MERS-CoV infection has led decision-makers to consider 62 dromedary vaccination as part of MERS-CoV prevention interventions (2). Dromedary-targeted

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Additionally, although whole-virus isolation and culture is necessary to confirm whether the shedding 78 is infectious, detection of viral RNA through RT-PCR can be used as a proxy for the prevalence and 79 distribution of infectious dromedaries (8-10).

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By conducting a qualitative synthesis of the study findings, considering reported heterogeneities, and 81 summarising the results of longitudinal studies of infection and immunity, we aim to assess the extent 82 of current understanding of MERS-CoV epidemiology in dromedaries, implications for control, and 83 gaps to be addressed going forward. We note that a similar systematic review of the literature up until

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May 2018 was unknowingly carried out in parallel to our own (11), with no discussion between the 85 two groups. Here, we confirm and update the results of the parallel review, discussing our results in 86 the context of potential animal vaccination and mathematical modelling of MERS-CoV in dromedary 87 camels.  f. neutralisation at dilution >1:80 gave 15% seropositivity but regional range only available for ELISA results -reported accordingly 138 g. study also tested different site-types but measured RNA in serum sample rather than nasal swab so this was not included 139 h. range is across weeks rather than regions 140 i. both (66) and (65) Fig 3).

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Although seroprevalence was 80-100% in adult dromedaries in most populations across the Middle   Three studies have found dromedaries to be shedding MERS-CoV RNA despite having high 266 antibody titres months or weeks prior to detectable infection. Both older animals whose 267 antibodies reflect past exposure (29,76,79), and young calves whose high antibody titres 268 were maternally-acquired immediately post-partum, became infected (79).

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One study directly observed recurring infection amongst a herd of dromedaries in Egypt.

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Four animals were shedding 1-3 months prior to a herd-wide epidemic in which they were  Age-dependent seroprevalence patterns suggest that the higher prevalence of viral shedding 311 in juveniles compared with adults is likely due to immunological naivety. The age-312 distribution of reported infections synthesised here, suggests that contact with juveniles may 313 pose greater risks of human transmission than adults, making them potential targets for 314 vaccination. However, frequency of human contact with dromedaries may also be animal-  respiratory syndrome coronavirus specific antibodies in naturally exposed Israeli llamas, 543 alpacas and camels. One Health. 2018;5:65-8. 544